Involvement of β3-adrenoceptors in mouse urinary bladder function: Role in detrusor muscle relaxation and micturition reflex

Jul 22, 2009European journal of pharmacology

Role of beta(3)-adrenoceptors in relaxing bladder muscle and controlling urination in mice

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Abstract

The beta(3)-adrenoceptor agonist CL316,243 decreased basal tone and spontaneous activity of mouse urinary bladder smooth muscle by 53±7% at 3 µM.

CL316,243 inhibited electrical field stimulation-induced contractions of the detrusor muscle, with a pEC(50) of 7.0±0.2.
The beta(3)-adrenoceptor antagonist SR59230A significantly blocked the relaxing effects of CL316,243 on both basal tone and neurogenic contractions.
L748,337 also inhibited the effects of CL316,243 on neurogenic contractions in a concentration-dependent manner, with a pK(B) of 6.8.
In vivo, intravenous administration of CL316,243 increased bladder capacity and threshold pressure without altering bladder compliance.
CL316,243 reduced the amplitude of both micturition and non-voiding contractions in anesthetized mice.

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beta(3)-adrenoceptor activation produces relaxation of human urinary bladder smooth muscle (detrusor). Therefore, beta(3)-adrenoceptor agonism is being investigated as a new therapeutic strategy for the treatment of overactive bladder. The aim of the current study was to identify the functional presence of beta(3)-adrenoceptors in mouse isolated urinary bladder using the selective beta(3)-adrenoceptor agonist CL316,243 and antagonists SR59230A and L748,337. The effects of CL316,243 on basal tone, spontaneous activity and electrical field stimulation (EFS)-induced contractions were investigated using in vitro techniques, while the in vivo effects of intravenously administered CL316,243 on the micturition reflex were investigated using cystometry. CL316,243 decreased basal tone (pEC(50)=6.4+/-0.4) as well as spontaneous activity (53+/-7% at 3 microM) and inhibited EFS-induced contractions (pEC(50)=7.0+/-0.2) of the detrusor muscle. The beta(3)-adrenoceptor antagonist SR59230A (1 microM) significantly inhibited the relaxing effects of CL316,243 on basal tone and neurogenic contractions (pA(2)=7.0 and 7.2, respectively). Another beta(3)-adrenoceptor antagonist L748,337 (1-10 microM) significantly blocked the CL316,243-evoked inhibition of neurogenic contractions in a concentration-dependent manner (pK(B)=6.8), while the selective beta(2)-adrenoceptor antagonist ICI118,551(30 nM) had no effect. In anesthetized mice, CL316,243 (0.03 and 0.1 mg/kg, i.v.) significantly increased bladder capacity and threshold pressure without a modification of bladder compliance. Moreover, it induced a significant decrease in the amplitude of both micturition and non-voiding contractions. Based on the current results obtained using the beta(3)-adrenoceptor agonist CL316,243 (as well as various beta-adrenoceptor antagonists), functional beta(3)-adrenoceptors appear to be present in mouse urinary bladder.

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Involvement of β3-adrenoceptors in mouse urinary bladder function: Role in detrusor muscle relaxation and micturition reflex

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